A To-Do List at Diagnosis of Systemic Sclerosis with Positive Anti-RNA Polymerase III Antibodies

ObjectiveScleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC.MethodsARA-positive patients (n = 99) with at least 5 years’ follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort.ResultsAnalysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 × 10−5), CTNND2 (rs1859082; P = 5.58 × 10−5), HECW2 (rs16849716; P = 1.2 × 10−4), and GPATCH2L (rs935332; P = 4.92 × 10−5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP.ConclusionIncreased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.

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RNA Polymerase III Antibody Positive Systemic Sclerosis with Cystic Interstitial Lung Disease and Pulmonary Hypertension

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3118 ◽

2019 ◽

Author(s):

A. Abdou ◽

A. Kotecha ◽

M. Mandeel ◽

V. Hannosh ◽

G. Krishnamoorthy

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Rna Polymerase ◽

Lung Disease ◽

Rna Polymerase Iii ◽

Polymerase Iii

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Malignancies in Italian Patients with Systemic Sclerosis Positive for Anti-RNA Polymerase III Antibodies

The Journal of Rheumatology ◽

10.3899/jrheum.101144 ◽

2011 ◽

Vol 38 (7) ◽

pp. 1329-1334 ◽

Cited By ~ 66

Author(s):

PAOLO AIRO’ ◽

ANGELA CERIBELLI ◽

ILARIA CAVAZZANA ◽

MARA TARABORELLI ◽

STEFANIA ZINGARELLI ◽

...

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Temporal Relationship ◽

Rna Polymerase Iii ◽

Patients With Cancer ◽

Polymerase Iii ◽

Number Of Patients ◽

I 11 ◽

Anticentromere Antibodies ◽

Close Temporal Relationship

Objective.To evaluate the frequency of malignancies in Italian patients with systemic sclerosis (SSc) and anti-RNA polymerase III (RNAP III), antitopoisomerase I (topo I), or anticentromere antibodies (ACA); and to characterize the temporal relationship between the 2 diseases, in order to confirm data suggesting a close temporal relationship between the onset of SSc and malignancy in American patients with anti-RNAP III antibodies.Methods.From a cohort of 466 consecutive SSc patients, 360 Italians with isolated positivity for anti-RNAP III (n = 16), anti-topo I (n = 101), or ACA (n = 243) were identified. Malignancy cases were divided according to their relationship with SSc onset into 3 categories: preceding, synchronous with, or metachronous to the onset of SSc (diagnosed more than 6 months before; 6 months before to 12 months after; and more than 12 months after onset of SSc, respectively).Results.Malignancies were more frequent in the anti-RNAP III group (7/16 patients), than in the anti-topo I (11/101) and ACA groups (21/243) (p < 0.001). This difference was accounted for by the number of patients with cancer synchronous to the onset of SSc (3/16 in the anti-RNAP III group vs 0/101 in the anti-topo I and 1/243 in the ACA group; p < 0.001), whereas neither the number of malignancies preceding nor those metachronous to the onset of SSc was significantly different between the groups.Conclusion.In a cohort of Italian patients with SSc we observed a significant association between malignancies synchronous to SSc onset and positivity for anti-RNAP III antibodies, similar to that described in American patients with SSc.

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Anti-Centromere Antibody Positivity in a Patient with Generalized Morphea

Case Reports in Dermatology ◽

10.1159/000493180 ◽

2018 ◽

Vol 10 (3) ◽

pp. 226-230

Author(s):

Fumi Miyagawa ◽

Anna Nakajima ◽

Yasuhiro Akai ◽

Hideo Asada

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Rna Polymerase Iii ◽

Skin Lesions ◽

Histological Findings ◽

Skin Manifestations ◽

Polymerase Iii ◽

Oral Steroids ◽

Antibody Positivity

We report the case of a 45-year-old female with generalized morphea (GM), who exhibited positivity for the anti-centromere antibody (Ab). She frequently developed multiple sclerotic skin lesions, whose histological findings were compatible with morphea. She demonstrated favorable responses to topical and oral steroids. Cases of GM associated with systemic sclerosis (SSc)-specific Abs (anti-Scl-70 Ab, anti-centromere Ab, and anti-RNA polymerase III Ab) have rarely been reported. The previously reported GM cases involving anti-SSc-specific Abs exhibited some skin manifestations of SSc, such as nailfold capillary changes. However, our case did not show any signs of SSc or limited cutaneous SSc. More cases are needed to clarify whether GM with SSc-specific Abs leads to SSc.

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OP0055 Anti-RNA Polymerase III Antibodies in Patients with Systemic Sclerosis: A Eustar Multicenter Collaborative Study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.1728 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 88.1-88

Author(s):

M.G. Lazzaroni ◽

E. Colombo ◽

I. Cavazzana ◽

O. Distler ◽

R. Hesselstrand ◽

...

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Rna Polymerase Iii ◽

Collaborative Study ◽

Polymerase Iii

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Prevalence, Correlates and Outcomes of Gastric Antral Vascular Ectasia in Systemic Sclerosis: A EUSTAR Case-control Study

The Journal of Rheumatology ◽

10.3899/jrheum.130386 ◽

2013 ◽

Vol 41 (1) ◽

pp. 99-105 ◽

Cited By ~ 56

Author(s):

Etienne Ghrénassia ◽

Jérome Avouac ◽

Dinesh Khanna ◽

Chris T. Derk ◽

Oliver Distler ◽

...

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Rna Polymerase Iii ◽

Scleroderma Renal Crisis ◽

Gastric Antral Vascular Ectasia ◽

Vascular Ectasia ◽

Polymerase Iii ◽

European League Against Rheumatism ◽

Vascular Phenotype ◽

Renal Crisis

Objective.To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE).Methods.We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes.Results.Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9–82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1–0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2–21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1–113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01).Conclusion.GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

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